tbuckley/cabot-search huggingface dataset:
A retrospective cohort study predicting and validating impact of the COVID-19 pandemic in individuals with chronic kidney disease
Authors: Ashkan Dashtban, Mehrdad A. Mizani, Spiros Denaxas, Dorothea Nitsch, Jennifer Quint, Richard Corbett, Jil B. Mamza, Tamsin Morris, Mamas Mamas, Deborah A. Lawlor, Kamlesh Khunti, Cathie Sudlow, Harry Hemingway, Amitava Banerjee
Journal: Kidney International (2022)

Chronic kidney disease (CKD) is associated with increased risk of baseline mortality and severe COVID-19, but analyses across CKD stages, and comorbidities are lacking. In prevalent and incident CKD, we investigated comorbidities, baseline risk, COVID-19 incidence, and predicted versus observed one-year excess death. In a national dataset (NHS Digital Trusted Research Environment [NHSD TRE]) for England encompassing 56 million individuals), we conducted a retrospective cohort study (March 2020 to March 2021) for prevalence of comorbidities by incident and prevalent CKD, SARS-CoV-2 infection and mortality. Baseline mortality risk, incidence and outcome of infection by comorbidities, controlling for age, sex and vaccination were assessed. Observed versus predicted one-year mortality at varying population infection rates and pandemic-related relative risks using our published model in pre-pandemic CKD cohorts (NHSD TRE and Clinical Practice Research Datalink [CPRD]) were compared. Among individuals with CKD (prevalent:1,934,585, incident:144,969), comorbidities were common (73.5% and 71.2% with one or more condition[s] in respective data sets, and 13.2% and 11.2% with three or more conditions, in prevalent and incident CKD), and associated with SARS-CoV-2 infection, particularly dialysis/transplantation (odds ratio 2.08, 95% confidence interval 2.04-2.13) and heart failure (1.73, 1.71-1.76), but not cancer (1.01, 1.01-1.04). One-year all-cause mortality varied by age, sex, multi-morbidity and CKD stage. Compared with 34,265 observed excess deaths, in the NHSD-TRE and CPRD databases respectively, we predicted 28,746 and 24,546 deaths (infection rates 10% and relative risks 3.0), and 23,754 and 20,283 deaths (observed infection rates 6.7% and relative risks 3.7). Thus, in this largest, national-level study, individuals with CKD have a high burden of comorbidities and multi-morbidity, and high risk of pre-pandemic and pandemic mortality. Hence, treatment of comorbidities, non-pharmaceutical measures, and vaccination are priorities for people with CKD and management of long-term conditions is important during and beyond the pandemic.
Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia
Authors: Emily Connell, Gwenaelle Le Gall, Matthew G. Pontifex, Saber Sami, John F. Cryan, Gerard Clarke, Michael Müller, David Vauzour
Journal: Molecular Neurodegeneration (2022)

A consequence of our progressively ageing global population is the increasing prevalence of worldwide age-related cognitive decline and dementia. In the absence of effective therapeutic interventions, identifying risk factors associated with cognitive decline becomes increasingly vital. Novel perspectives suggest that a dynamic bidirectional communication system between the gut, its microbiome, and the central nervous system, commonly referred to as the microbiota-gut-brain axis, may be a contributing factor for cognitive health and disease. However, the exact mechanisms remain undefined. Microbial-derived metabolites produced in the gut can cross the intestinal epithelial barrier, enter systemic circulation and trigger physiological responses both directly and indirectly affecting the central nervous system and its functions. Dysregulation of this system (i.e., dysbiosis) can modulate cytotoxic metabolite production, promote neuroinflammation and negatively impact cognition. In this review, we explore critical connections between microbial-derived metabolites (secondary bile acids, trimethylamine-N-oxide (TMAO), tryptophan derivatives and others) and their influence upon cognitive function and neurodegenerative disorders, with a particular interest in their less-explored role as risk factors of cognitive decline.
Peer support for discharge from inpatient mental health care – Authors' reply
Authors: Steve Gillard, Sally Barlow, Stephen Bremner, Rhiannon Foster, Sarah Gibson, Lucy Goldsmith, Andrew Healey, Mike Lucock, Jacqueline Marks, Akshaykumar Patel, Shalini Patel, Stefan Priebe, Miles Rinaldi, Alan Simpson, Michael Ussher, Sarah White
Journal: The Lancet Psychiatry (2022)
Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022
Authors: Sonja Pleininger, Alexander Indra, Daniel Golparian, Florian Heger, Stefanie Schindler, Susanne Jacobsson, Stefan Heidler, Magnus Unemo
Journal: Eurosurveillance (2022)

We describe a gonorrhoea case with ceftriaxone plus high-level azithromycin resistance. In April 2022, an Austrian heterosexual male was diagnosed with gonorrhoea after sexual intercourse with a female sex worker in Cambodia. Recommended treatment with ceftriaxone (1 g) plus azithromycin (1.5 g) possibly failed. Worryingly, this is the second strain in an Asian Neisseria gonorrhoeae genomic sublineage including high-level azithromycin-resistant strains that developed ceftriaxone resistance by acquisition of mosaic penA-60.001. Enhanced resistance surveillance and actions are imperative to prevent spread.
Anatomic patterns and clinical significance of gastrocolic trunk of Henlé in laparoscopic right colectomy for colon cancer: Results of the HeLaRC trial
Authors: Zirui He, Chunkang Yang, Dechang Diao, Deqing Wu, Abe Fingerhut, Yueming Sun, Yuan Gao, Nan Wang, Ang Li, Weidong Tong, Peirong Ding, Yi Xiao, Xiaojun Zhou, Zhangfa Song, Su Yan, Hongwei Yao, Wenjian Meng, Kejian Huang, Donglei Zhou, Anlong Zhu, Hao Wang, Yiming Zhou, Xinxiang Li, Liang Kang, Xuan Zhao, Hao Su, Minhua Zheng, Kai Ye, Quan Wang, Yincong Guo, Yun Lu, Bo Feng
Journal: International Journal of Surgery (2022)
The Kinetics and (Dys)kinetics of Cancer Chronotherapy
Authors: Jeffrey M. Field, Amita Sehgal
Journal: Cancer Research (2022)

Abstract Circadian rhythms are the daily cycles that time almost all aspects of physiology, but treatments of the clock or by the clock are rarely tested in the clinic. We develop a framework for identifying interventions that may benefit from administration at the appropriate time of day (chronotherapy). Typically, pharmacokinetics is an important consideration for chronotherapy, with short half-life drugs deemed optimal for such treatments. However, recent data suggest long-lived antibodies can show time-of-day specific effects. Examples include both tumor-targeted antibodies as well as immunotherapies with antibodies that activate T cells. Clues to the immunotherapy mechanism come from animal vaccination studies, which demonstrate circadian responses of T cells to a single dose that leads to long-lasting T-cell activation. Conversely, some studies have challenged the efficacy of chronotherapy, underscoring the need to rigorously investigate its application for each drug and tumor type.
An armed oncolytic virus enhances the efficacy of tumor-infiltrating lymphocyte therapy by converting tumors to artificial antigen-presenting cells in situ
Authors: Kai Ye, Fan Li, Ruikun Wang, Tianyi Cen, Shiyu Liu, Zhuoqian Zhao, Ruonan Li, Lili Xu, Guanmeng Zhang, Zhaoyuan Xu, Li Deng, Lili Li, Wei Wang, Alexey Stepanov, Yajuan Wan, Yu Guo, Yuanke Li, Yuan Wang, Yujie Tian, Alexander G. Gabibov, Yingbin Yan, Hongkai Zhang
Journal: Molecular Therapy (2022)

The full potential of tumor-infiltrating lymphocyte (TIL) therapy has been hampered by the inadequate activation and low persistence of TILs, as well as inefficient neoantigen presentation by tumors. We transformed tumor cells into artificial antigen-presenting cells (aAPCs) by infecting them with a herpes simplex virus 1 (HSV-1)-based oncolytic virus encoding OX40L and IL12 (OV-OX40L/IL12) to provide local signals for optimum T cell activation. The infected tumor cells displayed increased expression of antigen-presenting cell-related markers and induced enhanced T cell activation and killing in coculture with TILs. Combining OV-OX40L/IL12 and TIL therapy induced complete tumor regression in patient-derived xenograft and syngeneic mouse tumor models and elicited an antitumor immunological memory. In addition, the combination therapy produced aAPC properties in tumor cells, activated T cells, and reprogrammed macrophages to a more M1-like phenotype in the tumor microenvironment. This combination strategy unleashes the full potential of TIL therapy and warrants further evaluation in clinical studies. The full potential of tumor-infiltrating lymphocyte (TIL) therapy has been hampered by the inadequate activation and low persistence of TILs, as well as inefficient neoantigen presentation by tumors. We transformed tumor cells into artificial antigen-presenting cells (aAPCs) by infecting them with a herpes simplex virus 1 (HSV-1)-based oncolytic virus encoding OX40L and IL12 (OV-OX40L/IL12) to provide local signals for optimum T cell activation. The infected tumor cells displayed increased expression of antigen-presenting cell-related markers and induced enhanced T cell activation and killing in coculture with TILs. Combining OV-OX40L/IL12 and TIL therapy induced complete tumor regression in patient-derived xenograft and syngeneic mouse tumor models and elicited an antitumor immunological memory. In addition, the combination therapy produced aAPC properties in tumor cells, activated T cells, and reprogrammed macrophages to a more M1-like phenotype in the tumor microenvironment. This combination strategy unleashes the full potential of TIL therapy and warrants further evaluation in clinical studies.
Artificial Intelligence for Emerging Technology in Surgery: Systematic Review and Validation
Authors: Ephraim Nwoye, Wai Lok Woo, Bin Gao, Tobenna Anyanwu
Journal: IEEE Reviews in Biomedical Engineering (2022)

Surgery is a high-risk procedure of therapy and is associated to post trauma complications of longer hospital stay, estimated blood loss and long duration of surgeries. Reports have suggested that over 2.5% patients die during and post operation. This paper is aimed at systematic review of previous research on artificial intelligence (AI) in surgery, analyzing their results with suitable software to validate their research by obtaining same or contrary results. Six published research articles have been reviewed across three continents. These articles have been re-validated using software including SPSS and MedCalc to obtain the statistical features such as the mean, standard deviation, significant level, and standard error. From the significant values, the experiments are then classified according to the null (p < 0.05) or alternative (p>0.05) hypotheses. The results obtained from the analysis have suggested significant difference in operating time, docking time, staging time, and estimated blood loss but show no significant difference in length of hospital stay, recovery time and lymph nodes harvested between robotic assisted surgery using AI and normal conventional surgery. From the evaluations, this research suggests that AI-assisted surgery improves over the conventional surgery as safer and more efficient system of surgery with minimal or no complications.
Redefining critical illness
Authors: David M. Maslove, Benjamin Tang, Manu Shankar-Hari, Patrick R. Lawler, Derek C. Angus, J. Kenneth Baillie, Rebecca M. Baron, Michael Bauer, Timothy G. Buchman, Carolyn S. Calfee, Claudia C. dos Santos, Evangelos J. Giamarellos-Bourboulis, Anthony C. Gordon, John A. Kellum, Julian C. Knight, Aleksandra Leligdowicz, Daniel F. McAuley, Anthony S. McLean, David K. Menon, Nuala J. Meyer, Lyle L. Moldawer, Kiran Reddy, John P. Reilly, James A. Russell, Jonathan E. Sevransky, Christopher W. Seymour, Nathan I. Shapiro, Mervyn Singer, Charlotte Summers, Timothy E. Sweeney, B. Taylor Thompson, Tom van der Poll, Balasubramanian Venkatesh, Keith R. Walley, Timothy S. Walsh, Lorraine B. Ware, Hector R. Wong, Zsolt E. Zador, John C. Marshall
Journal: Nature Medicine (2022)
Risk of New-Onset Prostate Cancer for Metformin Versus Sulfonylurea Use in Type 2 Diabetes Mellitus: A Propensity Score–Matched Study
Authors: Yan Hiu Athena Lee, Jiandong Zhou, Jeremy Man Ho Hui, Xuejin Liu, Teddy Tai Loy Lee, Kyle Hui, Jeffrey Shi Kai Chan, Abraham Ka Chung Wai, Wing Tak Wong, Tong Liu, Kenrick Ng, Sharen Lee, Edward Christopher Dee, Qingpeng Zhang, Gary Tse
Journal: Journal of the National Comprehensive Cancer Network (2022)

The aim of this study was to compare the risks of new-onset prostate cancer between metformin and sulfonylurea users with type 2 diabetes mellitus (T2DM).This population-based retrospective cohort study included male patients with T2DM presenting to public hospitals/clinics in Hong Kong between January 1, 2000, and December 31, 2009. We only included patients prescribed either, but not both, metformin or sulfonylurea. All patients were followed up until December 31, 2019. The primary outcome was new-onset prostate cancer and the secondary outcome was all-cause mortality. One-to-one propensity score matching was performed between metformin and sulfonylurea users based on demographics, comorbidities, antidiabetic and cardiovascular medications, fasting blood glucose level, and hemoglobin A1c level. Subgroup analyses based on age and use of androgen deprivation therapy were performed.The final study cohort consisted of 25,695 metformin users (mean [SD] age, 65.2 [11.8] years) and 25,695 matched sulfonylurea users (mean [SD] age, 65.3 [11.8] years) with a median follow-up duration of 119.6 months (interquartile range, 91.7-139.6 months) after 1:1 propensity score matching of 66,411 patients. Metformin users had lower risks of new-onset prostate cancer (hazard ratio, 0.80; 95% CI, 0.69-0.93; P=.0031) and all-cause mortality (hazard ratio, 0.89; 95% CI, 0.86-0.92; P<.0001) than sulfonylurea users. Metformin use was more protective against prostate cancer but less protective against all-cause mortality in patients aged <65 years (P for trend <.0001 for both) compared with patients aged ≥65 years. Metformin users had lower risk of all-cause mortality than sulfonylurea users, regardless of the use of androgen deprivation therapy (P for trend <.0001) among patients who developed prostate cancer.Metformin use was associated with significantly lower risks of new-onset prostate cancer and all-cause mortality than sulfonylurea use in male patients with T2DM.
iRECIST and atypical patterns of response to immuno-oncology drugs
Authors: Jorge Luis Ramon-Patino, Sabine Schmid, Sally Lau, Lesley Seymour, Pierre-Olivier Gaudreau, Janice Juan Ning Li, Penelope Ann Bradbury, Emiliano Calvo
Journal: Journal for ImmunoTherapy of Cancer (2022)

With the advent of immunotherapy as one of the keystones of the treatment of our patients with cancer, a number of atypical patterns of response to these agents has been identified. These include pseudoprogression, where the tumor initially shows objective growth before decreasing in size, and hyperprogression, hypothesized to be a drug-induced acceleration of the tumor burden. Despite it being &gt;10 years since the first immune-oncology drug was approved, neither the biology behind these paradoxical responses has been well understood, nor their incidence, identification criteria, predictive biomarkers, or clinical impact have been fully described. Immune-based Response Evaluation Criteria in Solid Tumors (iRECIST) guidelines have been published as a revision to the RECIST V.1.1 criteria for use in trials of immunotherapeutics, and the iRECIST subcommittee (of the RECIST Working Group) is working on elucidating these aspects, with data sharing a current major challenge to move forward with this unmet need in immuno-oncology.
Convergent Clonal Evolution of Signaling Gene Mutations Is a Hallmark of Myelodysplastic Syndrome Progression
Authors: Andrew J. Menssen, Ajay Khanna, Christopher A. Miller, Sridhar Nonavinkere Srivatsan, Gue Su Chang, Jin Shao, Joshua Robinson, Michele O'Laughlin, Catrina C. Fronick, Robert S. Fulton, Kimberly Brendel, Sharon E. Heath, Raya Saba, John S. Welch, David H. Spencer, Jacqueline E. Payton, Peter Westervelt, John F. DiPersio, Daniel C. Link, Matthew J. Schuelke, Meagan A. Jacoby, Eric J. Duncavage, Timothy J. Ley, Matthew J. Walter
Journal: Blood Cancer Discovery (2022)

Abstract Progression from myelodysplastic syndromes (MDS) to secondary acute myeloid leukemia (AML) is associated with the acquisition and expansion of subclones. Our understanding of subclone evolution during progression, including the frequency and preferred order of gene mutation acquisition, remains incomplete. Sequencing of 43 paired MDS and secondary AML samples identified at least one signaling gene mutation in 44% of MDS and 60% of secondary AML samples, often below the level of standard sequencing detection. In addition, 19% of MDS and 47% of secondary AML patients harbored more than one signaling gene mutation, almost always in separate, coexisting subclones. Signaling gene mutations demonstrated diverse patterns of clonal evolution during disease progression, including acquisition, expansion, persistence, and loss of mutations, with multiple patterns often coexisting in the same patient. Multivariate analysis revealed that MDS patients who had a signaling gene mutation had a higher risk of AML progression, potentially providing a biomarker for progression. Significance: Subclone expansion is a hallmark of progression from MDS to secondary AML. Subclonal signaling gene mutations are common at MDS (often at low levels), show complex and convergent patterns of clonal evolution, and are associated with future progression to secondary AML. See related article by Guess et al., p. 316 (33). See related commentary by Romine and van Galen, p. 270. This article is highlighted in the In This Issue feature, p. 265
Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial
Authors: Manali Kamdar, Scott R Solomon, Jon Arnason, Patrick B Johnston, Bertram Glass, Veronika Bachanova, Sami Ibrahimi, Stephan Mielke, Pim Mutsaers, Francisco Hernandez-Ilizaliturri, Koji Izutsu, Franck Morschhauser, Matthew Lunning, David G Maloney, Alessandro Crotta, Sandrine Montheard, Alessandro Previtali, Lara Stepan, Ken Ogasawara, Timothy Mack, Jeremy S Abramson
Journal: The Lancet (2022)
Association of race/ethnicity with innate immune tumor microenvironment of children with B-acute lymphoblastic leukemia
Authors: Julie R Gilbert, Himalee S Sabnis, Roman Radzievski, Deon B Doxie, Deborah DeRyckere, Sharon M Castellino, Kavita Dhodapkar
Journal: Journal for ImmunoTherapy of Cancer (2022)

Black and Hispanic children with B-acute lymphoblastic leukemia (B-ALL) experience worse outcomes compared with their non-Hispanic white (NHW) counterparts. Immune-based approaches have begun to transform the therapeutic landscape in children with B-ALL. Recent studies identified several alterations in both innate and adaptive immune cells in children with B-ALL that may impact disease risk and outcome. However, the impact of racial/ethnic background on immune microenvironment is less studied, as children of minorities background have to date been severely under-represented in such studies. We performed high-dimensional analysis of bone marrow from 85 children with newly diagnosed B-ALL (Hispanic=29, black=18, NHW=38) using mass cytometry with 40 and 38-marker panels. Race/ethnicity-associated differences were most prominent in the innate immune compartment. Hispanic patients had significantly increased proportion of distinct mature CD57 +T-bet+DR+ NK cells compared with other cohorts. These differences were most apparent within standard risk (SR) patients with Hispanic SR patients having greater numbers of CD57 +NK cells compared with other cohorts (43% vs 26% p=0.0049). Hispanic and Black children also had distinct alterations in myeloid cells, with a significant increase in a population of non-classical activated HLA-DR +CD16+myeloid cells, previously implicated in disease progression, compared with NHW counterparts. Racial background also correlated with altered expression of inhibitory checkpoint PD-L1 on myeloid cells. There are surprisingly substantial race/ethnicity-based differences in innate immune cells of children with newly diagnosed B-ALL. These differences urge the need to enhance accrual of children from minorities background in immunetherapy trials and may impact their outcome following such therapy.
Comprehensive Serum Proteome Profiling of Cytokine Release Syndrome and Immune Effector Cell–Associated Neurotoxicity Syndrome Patients with B-Cell ALL Receiving CAR T19
Authors: Caroline Diorio, Rawan Shraim, Regina Myers, Edward M. Behrens, Scott Canna, Hamid Bassiri, Richard Aplenc, Chakkapong Burudpakdee, Fang Chen, Amanda M. DiNofia, Saar Gill, Vanessa Gonzalez, Michele P. Lambert, Allison Barz Leahy, Bruce L. Levine, Robert B. Lindell, Shannon L. Maude, J. Joseph Melenhorst, Haley Newman, Jessica Perazzelli, Alix E. Seif, Simon F. Lacey, Carl H. June, David M. Barrett, Stephan A. Grupp, David T. Teachey
Journal: Clinical Cancer Research (2022)

To study the biology and identify markers of severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in children after chimeric antigen receptor T-cell (CAR T) treatment.We used comprehensive proteomic profiling to measure over 1,400 serum proteins at multiple serial timepoints in a cohort of patients with B-cell acute lymphoblastic leukemia treated with the CD19-targeted CAR T CTL019 on two clinical trials.We identified fms-like tyrosine kinase 3 (FLT3) and mast cell immunoglobulin-like receptor 1 (MILR1) as preinfusion predictive biomarkers of severe CRS. We demonstrated that CRS is an IFNγ-driven process with a protein signature overlapping with hemophagocytic lymphohistiocytosis (HLH). We identified IL18 as a potentially targetable cytokine associated with the development of ICANS.We identified preinfusion biomarkers that can be used to predict severe CRS with a sensitivity, specificity, and accuracy superior to the current gold standard of disease burden. We demonstrated the fundamental role of the IFNγ pathway in driving CRS, suggesting CRS and carHLH are overlapping rather than distinct phenomena, an observation with important treatment implications. We identified IL18 as a possible targetable cytokine in ICANS, providing rationale for IL18 blocking therapies to be translated into clinical trials in ICANS.